Osteoarthritis is characterized by chronic degradation of articular cartilage in the afflicted joints. Histochemical and biochemical findins suggest that increased levels of lysosomal enzymes are associated with the breakdown of proteoglycans, the principal extracellular constituents. The enzymes responsible for the degradation of chondroitin sulfate, the primary glycosaminoglycan component of these proteoglycans in human articular cartilage, will be investigated. Aryl sulfatase A and B activities have been shown to be elevated in articular cartilage derived from individuals with osteoarthritis. Aryl sulfatase A, now identified as a cerebroside sulfatase, will be purified with a view to discerning differences in sulfated glycolipid metabolism in normal and pathologic tissue. In addition, we propose to isolate and purify aryl sulfatase B and will attempt to identify its physiological role in articular cartilage. In an effort to correlate chondroitin sulfate catabolism with the severity of the disease the intermediary and final degradation products of chondroitin sulfate will be characterized and the levels of these substances in a variety of normal and osteoarthritic cartilage specimens will be compared. Tissue culture systems will be employed to measure the effect of extracellular modulators on enzymes in the degradative pathway. In the broadest sense, this research is directed toward a better understanding of the regulation of sulfated proteoglycan and sulfated glycolipid metabolism under different physiological conditions with a view to facilitating early diagnosis and providing a rationale for non-surgical therapy in osteoarthritis.